Protein translocation and retro-translocation across the endoplasmic reticulum are crucial to inflammatory effector CD4+ T cell function.

Protein translocation and retro-translocation across the endoplasmic reticulum are crucial to inflammatory effector CD4+ T cell function. Cytokine. 2020 Mar 05;129:154944 Authors: Pradeep Yeola A, Akbar I, Baillargeon J, Mercy Ignatius Arokia Doss P, Paavilainen VO, Rangachari M Abstract Effector CD4+ T cells can be classified by the cytokines they secrete, with T helper 1 (Th1) cells generating interferon (IFN)γ and Th17 cells secreting interleukin (IL)-17. Both Th1 and Th17 cells are strongly implicated in the initiation and chronicity of autoimmune diseases such as multiple sclerosis. The endoplasmic reticulum (ER) has been implicated as a potentially crucial site in regulating CD4+ T cell function. Secretory and transmembrane proteins are shuttled into the ER via the Sec61 translocon, where they undergo appropriate folding; misfolded proteins are retro-translocated from the ER in a p97-dependent manner. Here, we provide evidence that both processes are crucial to the secretion of inflammatory cytokines from effector CD4+ T cells. The pan-ER inhibitor eeeyarestatin-1 (ESI), which interferes with both Sec61 translocation and p97 retro-translocation, inhibited secretion of interferon (IFN)γ, interleukin (IL)-2 and tumor necrosis factor (TNF)α from Th1 cells in a dose-dependent manner. Selective inhibition of Sec61 by Apratoxin A (ApraA) revealed that ER translocation is crucial for Th1 cytokine secretion, while inhibition of p97 ...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research